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Coverage criteria policies

Genetic Testing: Coagulation Disorders and Cardiovascular Risk Assessments

These services may or may not be covered by your HealthPartners plan. Please see your plan documents for your specific coverage information. If there is a difference between this general information and your plan documents, your plan documents will be used to determine your coverage.

Administrative Process

Prior authorization is required for genetic testing for coagulation disorders and genetic cardiovascular risk assessments, except for the following services:

  • Factor V Leiden (F5 p.Arg506Gln variant)
  • Prothrombin gene mutation (F2 G20210A variant)

For genetic testing related to arrhythmias and cardiomyopathies, see the Genetic Testing for Arrhythmias and Cardiomyopathies coverage policy.

For genetic testing related to reproductive planning, see the Genetic Testing: Carrier Screening, Prenatal Screening, Prenatal Diagnosis, and Infertility Evaluation coverage policy.

For pharmacogenetic testing, see the Genetic Testing: Pharmacogenetics coverage policy.

For non-genetic cardiovascular risk assessments, see the Cardiovascular Risk Assessments coverage policy.

Coverage

Indications that are covered

Single-gene and multiple-gene analysis for these conditions is covered when criteria 1-3 listed below are met:

  • Afibrinogenemia, hypofibrinogenemia, and dysfibrinogenemia (FGA, FGB, FGG genes)
  • Antithrombin deficiency
  • Factor V Leiden (F5 p.Arg506Gln variant)
  • Factor XI deficiency (FXI gene)
  • Hemophilia A (F8 gene)
  • Hemophilia B (F9 gene)
  • Prothrombin gene mutation (F2 G20210A variant)
  • Von Willebrand disease (type 2B, type 2N, or type 3)
  1. The test is ordered by a board-certified hematologist or medical geneticist, an advanced-practice nurse in hematology or genetics, or a provider specializing in thrombosis or coagulation disorders who is formally affiliated with a thrombosis or coagulation specialty clinic.
  2. The test is expected to directly impact management of a specific, clinically-suspected, coagulation disorder or to determine predisposition to a specific, inheritable, coagulation disorder.
  3. The member has a personal or family history consistent with the condition being evaluated.
Single-gene and multiple-gene analysis for familial hypercholesterolemia (FH) is covered when criteria 1-4 below are met:
  1. The test is ordered by a board-certified cardiologist, medical geneticist, or advanced practice nurse in genetics or cardiology.
  2. The member has received pre-test genetic counseling from a board-certified genetic counselor or medical geneticist who is not affiliated with the commercial genetic testing laboratory, if applicable.
  3. The test is recommended by a Clinical Lipid Specialist
  4. The test is ordered for any of the following indications:
  • Xanthomata and/or a clinical diagnosis of homozygous FH
  • Plasma total cholesterol >310 mg/dL in an adult or adult first-degree relative or >230 mg/dL in a child or child first degree-relative
  • Premature clinical coronary heart disease or sudden cardiac death in a first-degree relative
  • Testing of a first-degree relative of an individual with a known causative mutation
Peripheral blood cell gene expression profiling is covered when criteria 1-5 below are met:
  1. The test is ordered by a board-certified cardiologist, medical geneticist, or advanced practice nurse in genetics or cardiology.
  2. The test is expected to directly impact evaluation of chest pain or other symptoms of angina.
  3. The member is not currently taking steroids, immunosuppressive agents, or chemotherapeutic agents.
  4. The member does not currently have any of the following:
  • Diabetes
  • Suspected myocardial infarction or unstable angina
  • New York Heart Association (NYHA) Class III or IV congestive heart failure symptoms
  • Systemic infection or inflammatory condition
  1. The member does not have a history of any of the following:
  • Obstructive coronary artery disease
  • Coronary revascularization
  • Myocardial infarction or other acute coronary syndrome

Genetic testing for coagulation disorders and genetic cardiovascular risk assessments other than described above is subject for a review for medical necessity, based on current clinical literature and expert recommendations, unless listed below as an indication that is not covered.

Indications that are not covered

  1. Genetic testing for coagulation disorders and genetic cardiovascular risk assessments are not covered and are considered not medically necessary when test results will not directly impact the treatment, prevention, or management of a condition because the testing is not expected to restore or maintain the member’s health, prevent deterioration of the member’s condition, nor prevent the reasonably likely onset of a health problem, or detect an incipient problem.
  2. Repeat testing of a unique analyte using the identical method of analysis is not covered and is considered not medically necessary because it is not considered an appropriate frequency of care.
  3. Direct-to-consumer genetic testing is not covered and is considered not medically necessary because it is not within the practice parameters of the general medical community.
  4. The following services are considered not medically necessary because they are not considered appropriate types of services for the member’s condition:
  • Multiple-gene panels which include genes not associated with the specific condition under evaluation
  • Genetic testing for members with a clinical diagnosis of heterozygous familial hypercholesterolemia
  • Genetic testing for members with a clinical diagnosis of Von Willebrand disease other than type 2B, type 2N, or type 3
  • Genetic testing of relatives of an individual with a cardiovascular condition to determine cardiovascular risk, except as described above under Indications That Are Covered
  1. The following services are considered experimental/investigational when performed as cardiovascular risk assessments and/or as assessments related to coagulation disorders because reliable evidence does not permit conclusions concerning safety, effectiveness, or effect on health outcomes:
  • ACE gene analysis
  • AGT gene analysis
  • Apolipoprotein E (APOE) gene analysis
  • Circulating microRNA analysis
  • Factor XIIIA1 polymorphism testing
  • F2 gene variant analysis other than for the G20210A variant
  • F5 gene variant analysis other than for the p.Arg506Gln variant, including but not limited to HR2 haplotype analysis for members with hypercoagulability symptoms or for members who are heterozygous for the F5 p.Arg506Gln variant
  • Fibrinogen-beta (FGB) c.-455G>A polymorphism analysis
  • Interleukin 6-174 polymorphism analysis
  • Locus 9p21 single nucleotide polymorphism (SNP) analysis
  • MTHFR gene analysis
  • Peripheral blood cell gene expression profiling for members with diabetes, current myocardial infarction or unstable angina, NYHA Class III or IV congestive heart failure symptoms, systemic infection, or a systemic inflammatory condition or who are currently taking steroids, immunosuppressive agents, or chemotherapeutic agents

Definitions

Cardiovascular disease refers to conditions that involve narrowed or blocked blood vessels that can lead to conditions including heart attach (myocardial infarction), chest pain (angina), or stroke. Examples of these conditions are coronary artery disease (CAD), high blood pressure (hypertension), high blood cholesterol (hypercholesterolemia/hyperlipidemia), and congestive heart failure (CHF).

Clinical Lipid Specialist is a physician or related medical or allied health provider who has extended focused study in the treatment paradigms for management of dyslipidemia and has received certification in the care and management of patients affected by dyslipidemia and related disorders.

Coagulation is the process of blood clotting

Thrombosis is the formation of a blood clot inside a blood vessel

If available, codes are listed below for informational purposes only, and do not guarantee member coverage or provider reimbursement. The list may not be all-inclusive.

Code

Description

81238

F9 (coagulation factor IX) (eg, hemophilia B), full gene sequence

81240

F2 (prothrombin, coagulation factor II) (eg, hereditary hypercoagulability) gene analysis, 20210G>A variant

81241

F5 (coagulation factor V) (eg, hereditary hypercoagulability) gene analysis, Leiden variant

81291

MTHFR (5,10-methylenetetrahydrofolate reductase) (eg, hereditary hypercoagulability) gene analysis, common variants (eg, 677T, 1298C)

81493

Coronary artery disease, mRNA, gene expression profiling by real-time RT-PCR of 23 genes, utilizing whole peripheral blood, algorithm reported as a risk score

CPT Copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association

Products

This information is for most, but not all, HealthPartners plans. Please read your plan documents to see if your plan has limits or will not cover some items. If there is a difference between this general information and your plan documents, your plan documents will be used to determine your coverage. These coverage criteria may not apply to Medicare Products if Medicare requires different coverage. For more information regarding Medicare coverage criteria or for a copy of a Medicare coverage policy, contact Member Services at 952-883-7979 or 1-800-233-9645.

References

  1. Aleksova, A., Di Nucci, M., Gobbo, M., Bevilacqua, E., Pradella, P., Salam, K., . . . Sinagra, G. (2015). Factor-V HR2 haplotype and thromboembolic disease. Acta Cardiologica, 70, 707-711.
  2. Bauer, K. A. (2016a). Antithrombin deficiency. In: L. L. K. Leung & J. S. Timauer (Eds.). UpToDate. Waltham, MA: UpToDate.
  3. Bauer, K. A. (2016b). Factor V Leiden and activated protein C resistance. In: L. L. K. Leung & J. S. Timauer (Eds.). UpToDate. Waltham, MA: UpToDate.
  4. Bauer, K. A. (2016c). Prothrombin G20210A mutation. In: L. L. K. Leung & J. S. Timauer (Eds.). UpToDate. Waltham, MA: UpToDate.
  5. Berube, C. (2016a). Disorders of fibrinogen. In: L. L. K. Leung & J. S. Timauer (Eds.). UpToDate. Waltham, MA: UpToDate.
  6. Berube, C. (2016b). Factor XI deficiency. In: L. L. K. Leung & J. S. Timauer (Eds.). UpToDate. Waltham, MA: UpToDate.
  7. Chen, F., Zhao, X., Peng, J., Bo, L., Fan, B., & Ma, D. (2014). Integrated microRNA-mRNA analysis of coronary artery disease. Molecular Biology Reports, 41, 5505-5511.
  8. Daniels, S. E., Beineke, P., Rhees, B., McPherson, J. A., Kraus, W. E., Thomas, G. S., & Rosenberg, S. (2014). Biological and analytical stability of a peripheral blood gene expression score for obstructive coronary artery disease in the PREDICT and COMPASS studies. Journal of Cardiovascular Translational Research, 7, 615-622.
  9. De Ferranti, S. D., & Newburger, J. W. (2016). Dyslipidemia in children: Definition, screening, and diagnosis. In: D. R. Fulton & C. Armsby (Eds.). UpToDate. Waltham, MA: UpToDate.
  10. ECRI Institute. (2016). Corus CAD (CardioDx, Inc.) gene expression testing for assessing risk of obstructive coronary artery disease. Plymouth Meeting, PA: ECRI Institute.
  11. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. (2011). Recommendations from the EGAPP Working Group: Routine testing for Factor V Leiden (R506Q) and prothrombin (20210G>A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members. Genetics in Medicine, 13, 67-76.
  12. Grody, W. W., Griffin, J. H., Taylor, A. K., Korf, B. R., Heit, J. A., & ACMG Factor V Leiden Working Group. (2001). American College of Medical Genetics consensus statement on factor V Leiden mutation testing. Genetics in Medicine, 3, 139-148.
  13. Hayes, Inc. (2014). Von Willebrand factor (VWF) gene testing for von Willebrand disease. Philadelphia, PA: Hayes, Inc.
  14. Hayes, Inc. (2015a). Factor V (F5) HR2 haplotype testing for hypercoagulability. Philadelphia, PA: Hayes, Inc.
  15. Hayes, Inc. (2015b). Factor V Leiden (FVL) testing for venous thromboembolism (VTE), obstetrical complications, and oral contraceptive Use. Philadelphia, PA: Hayes, Inc.
  16. Hayes, Inc. (2015c). Factor XIIIA1 (F13A1) p.Val34Leu polymorphism testing. Philadelphia, PA: Hayes, Inc.
  17. Hayes, Inc. (2016a). Corus CAD. Philadelphia, PA: Hayes, Inc.
  18. Hayes, Inc. (2016b). Fibrinogen-Beta (FGB) c.-455G>A polymorphism testing in cardiovascular disease. Philadelphia, PA: Hayes, Inc.
  19. Herman, L., Froelich, J., Kanelos, D., St. Amant, R., Yau, M., Rhees, B., . . . McPherson, J. (2014). Utility of a genomic-based, personalized medicine test in patients presenting with symptoms suggesting coronary artery disease. Journal of the American Board of Family Medicine, 27, 258-267.
  20. Hoots, W. K., & Shapiro, A. D. (2014). Clinical manifestations and diagnosis of hemophilia. In: L. L. K. Leung, D. H. Mahoney, Jr., & J. S. Timauer (Eds.). UpToDate. Waltham, MA: UpToDate.
  21. Jin, Y., Wang, Q., Wang, G., Zhang, X., Yan, B., & Hu, W. (2014). Common polymorphisms in the interleukin-6 gene and myocardial infarction risk: a meta-analysis. Genetic Testing and Molecular Biomarkers, 18, 330-340.
  22. Jorgensen, A. B., Frikke-Schmidt, R., Nordestgaard, B. G., & Tybjaerg-Hansen, A. (2014). Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. New England Journal of Medicine, 371, 32-41.
  23. Kazmi, N., & Gaunt, T. R. (2016). Diagnosis of coronary heart diseases using gene expression profiling; stable coronary artery disease; cardiac ischemia with and without myocardial necrosis. PLoS One, 11, e0149475.
  24. Li, K., Zhang, T., Fan, H., Li, Q., Ito, W., Torzewski, J., . . . Liu, Z. (2014). The analysis of microRNA expression profiling for coronary artery disease. Cardiology, 127, 62-69.
  25. Mannucci, P. M. (2016). Rare inherited coagulation disorders. In: L. L. K. Leung & J. S. Timauer (Eds.). UpToDate. Waltham, MA: UpToDate.
  26. Munir, M. S., Wang, Z., Alahdab, F., Steffen, M. W., Erwin, P. J., Kullo, I. J., & Murad, M. H. (2014). The association of 9p21.3 locus with coronary atherosclerosis: a systematic review and meta-analysis. BMC Medical Genetics, 15, 66-75.
  27. Ng, C., Motto, D. G., & Di Paola, J. (2015). Diagnostic approach to von Willebrand disease. Blood, 125, 2029-2037.
  28. Ni, X., & Zhang, J. (2014). Association between 9p21 genomic markers and ischemic stroke risk: evidence based on 21 studies. PLoS One, 9, e90255.
  29. Nichols, W. L., Hultin, M. B., James, A. H., Manco-Johnson, M. J., Montgomery, R. R., Rick, M. E., . . . Yawn, B. P. (2008). Von Willebrand disease (VWD): Evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia, 14, 171-232.
  30. Patel, R. S., Asselbergs, F. W., Quyyumi, A. A., Palmer, T. M., Finan, C. I., Tragante, V., . . . Holmes, M. V. (2014). Genetic variants at chromosome 9p21 and risk of first versus subsequent coronary heart disease events: a systematic review and meta-analysis. Journal of the American College of Cardiology, 63, 2234-2245.
  31. Peng, L., Chun-guang, Q., Bei-fang, L., Xue-zhi, D., Zi-hao, W., Yun-fu, L., . . . Zhen-wen, H. (2014). Clinical impact of circulating miR-133, miR-1291, and miR-633b in plasma of patients with acute myocardial infarction. Diagnostic Pathology, 9, 89-95.
  32. Press, R. D., Bauer, K. A., Kujovich, J. L., & Heit, J. A. (2002). Clinical utility of factor V Leiden (R506Q) testing for the diagnosis and management of thromboembolic disorders. Archives of Pathology and Laboratory Medicine, 126, 1304-1318.
  33. Smith, T. W., & Morgan, J. P. (2015). Actions of angiotensin II on the heart. In: W. S. Colucci & S. B. Yeon (Eds.). UpToDate: Waltham, MA: UpToDate.
  34. Spoto, B., Mattace-Raso, F., Sijbrands, E., Leonardis, D., Testa, A., Pisano, A., . . . Zoccali, C. (2015). Association of IL-6 and a functional polymorphism in the IL-6 gene with cardiovascular events in patients with CKD. Clinical Journal of the American Society of Nephrology, 10, 232-240.
  35. Stevens, S. M., Woller, S. C., Bauer, K. A., Kasthuri, R., Cushman, M., Streiff, M., . . . Doukets, J. D. (2016). Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. Journal of Thrombosis and Thrombolysis, 41, 154-164.
  36. Szpakowicz, A., Kiliszek, M., Pepinski, W., Waszkiewicz, E., Franaszczyk, M., Skawronska, M., . . . Kaminski, K. A. (2014). Polymorphsim of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction. PLoS One, 9, e104635.
  37. TG and HDL Working Group of the Exome Sequencing Project, National Heart, Lung, and Blood Institute. (2014). Loss-of-function mutations in APOC3, triglycerides, and coronary disease. New England Journal of Medicine, 371, 22-31.
  38. Van Cott, E. M., Laposata, M., & Prins, M. H. (2002). Laboratory evaluation of hypercoagulability with venous or arterial thrombosis. Archives of Pathology and Laboratory Medicine, 126, 1281-1295.
  39. Voros, S., Elashoff, M. R., Wingrove, J. A., Budoff, M. J., Thomas, G. S., & Rosenberg, S. (2014). A peripheral blood gene expression score is associated with atherosclerotic plaque burden and stenosis by cardiovascular CT-angiography: results from the PREDICT and COMPASS studies. Atherosclerosis, 233, 284-290.
  40. Wang, J., Pei, Y., Zhong, Y., Jiang, S., Shao, J., & Gong, J. (2014). Altered serum microRNAs as novel diagnostic biomarkers for atypical coronary artery disease. PLoS One, 9, e107012.
  41. Wilson, P. W. F. (2017). Overview of the possible risk factors for cardiovascular disease. In: C. P. Cannon & B. C. Downey (Eds.). UpToDate. Waltham, MA: UpToDate.
  42. Yang, Y., Cai, Y., Wu, G., Chen, X., Liu, Y., Wang, X., . . . Zeng, C. (2015). Plasma long non-coding RNA, CoroMarker, a novel biomarker for diagnosis of coronary artery disease. Clinical Science, 129, 675-685.
  43. Zeng, W., Tang, L., Jian, X. R., Li, Y. Q., Guo, T., Wang, Q. Y., . . . Hu, Y. (2015). Genetic analysis should be included in clinical practice when screening for antithrombin deficiency. Thrombosis and Haemostasis, 113, 262-271.
  44. Zhao, W., Smith, J. A., Mao, G., Fornage, M., Peyser, P. A., Sun, Y. V., . . . Kardia, S. L. (2015). The cis and trans effects of the risk variants of coronary artery disease in the Chr9p21 region. BMC Medical Genomics, 8, 21-32.
  45. Zhu, G. F., Yang, L. X., Guo, R. W., Liu, H., Shi, Y. K., Ye, J. S., & Yang, Z. H. (2014). MicroRNA-155 is inversely correlated with severity of coronary stenotic lesions calculated by the Gensini score. Coronary Artery Disease, 25, 304-310.

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Policy activity

  • 06/21/2016 - Date of origin
  • 07/01/2017 - Effective date
Review date
  • 04/2017
Revision date
  • 04/03/2017

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